The SKVs are a group of avian retroviruses possessing the common oncogene, ski. The present studies will probe the activity of the ski gene by examining the phenotype of SKV-infected chicken and quail embryo cells. A nondefective SKV, constructed from molecularly cloned DNAs will be the starting material for the construction of mutant viruses which will be used to dissect the biological activities of the ski gene and the biochemical properties of its encoded protein. Related techniques will be employed to generate recombinant viral genomes using fragments of the cellular proto-oncogene c-ski to replace deleted portions of the viral homolog. The goal of these studies is to identify the regions of the viral gene that are responsible for its transforming capacity and to determine which properties and functions of the gene relate to its activation as an oncogene. Additional studies will be performed to determine the structure and study the expression of c-ski. These studies will explore its expression with respect to the cell division cycle and during chicken embryogenesis. The possible involvement of ski in human malignancy will be studied by cloning the human homolog of ski and examining the possible rearrangement or amplification of the gene in DNAs from human tumors.